Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns

Study Description

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Brief Summary:

Bronchopulmonary dysplasia (BPD) is a serious lung condition that affects premature newborns. The condition involves abnormal development of lung tissue and is characterized by inflammation and scarring in the lungs. Treatment with inhaled nitric oxide (iNO) may reduce the incidence of BPD and another commonly associated condition called pulmonary hypertension, which is high blood pressure in the vessels carrying blood to the lungs.. This study will determine if early treatment with low-dose iNO reduces the incidence of BPD, pulmonary hypertension, and death in premature newborns.

Condition or disease	Intervention/treatment	Phase
Bronchopulmonary Dysplasia	Drug: Inhaled Nitric Oxide (iNO); Drug: Nitrogen (placebo)	Phase 2

Detailed Description:

BPD is a serious lung condition that primarily affects premature newborns and newborns with low birth weights. iNO has been proven to be a safe and effective treatment for pulmonary hypertension and hypoxemic respiratory failure—both of which are abnormal lung conditions—in full-term newborns. However, in babies born prematurely, the effects of iNO on lung function are not well defined. Also, previous studies have mainly examined whether iNO reduces the incidence of BPD in newborns who are on mechanical ventilation. However, intubation and mechanical ventilation of premature newborns is now increasingly being avoided, and non-invasive support, including the use of nasal continuous positive airway pressure (NCPAP), is being used. Early treatment with low-dose iNO may reduce the incidence of BPD in premature newborns who do not require mechanical ventilation and intubation after delivery. The purpose of this study is to determine if low-dose, non-invasive iNO reduces the risk of BPD, pulmonary hypertension, and death in premature newborns who do not require mechanical ventilation.

This study will enroll premature newborns who require extra oxygen but do not require intubation or mechanical ventilation for respiratory failure in the first 72 hours of life. Participants will be randomly assigned to receive low-dose, non-invasive iNO or nitrogen (placebo) during their hospital stay. While hospitalized, participants' heart rate, blood oxygen level breathing rate, blood pressure, and medications will be monitored, and blood collection will occur at various times. Monitoring will continue until participants are 30 weeks corrected gestational age or for at least 14 days if participants are born at 29 weeks or more. All participants will undergo an ultrasound of the head when they are 7 days, 28 days, and 36 weeks of age. They will undergo an echocardiogram, which is an ultrasound of the heart, at 7 and 21 days of age and 4 weeks before the original expected due date. A chest x-ray will be performed before hospital discharge, and a breathing status test will be performed either 4 weeks before participants' original expected due date or before hospital discharge. Follow-up study visits will occur at Years 1 and 2, and will include a physical examination and developmental and behavioral testing. Another echocardiogram will also be performed at the Year 1 visit.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	124 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Prevention
Official Title:	Examining the Use of Non-Invasive Inhaled Nitric Oxide to Reduce Chronic Lung Disease in Premature Newborns
Study Start Date :	January 2007
Actual Primary Completion Date :	July 2014
Actual Study Completion Date :	December 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Inhaled Nitric Oxide (iNO); Participants will receive a low concentration of iNO until they are 30 weeks corrected gestational age or for 14 days if they were born at 29 weeks or more.	Drug: Inhaled Nitric Oxide (iNO); iNO will be delivered using the iNOVent device to provide 10 ppm proximally (yielding approximately 5 ppm to the posterior pharynx).
Placebo Comparator: Nitrogen (placebo); Participants will receive nitrogen (placebo) while in the hospital.	Drug: Nitrogen (placebo); Nitrogen will be delivered using the iNOVent device to provide 10 ppm proximally (yielding approximately 5 ppm to the posterior pharynx).

Outcome Measures

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Primary Outcome Measures :

1. Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality [ Time Frame: Week 36 or earlier, if participants are discharged from the hospital ]
   Number of participants that developed bronchopulmonary dysplasia and/or that died
2. Combined Endpoint of Bronchopulmonary Dysplasia (BPD) or Mortality Stratified by Birth Weight [ Time Frame: Randomization to discharge ]
   Number of participants that developed bronchopulmonary dysplasia and/or that died, stratified by birth weight (grams)

Secondary Outcome Measures :

1. Severity of Bronchopulmonary Dysplasia (BPD) [ Time Frame: 36 weeks corrected gestational age ]
   Assessment of the severity of BPD as defined by the oxygen reduction test
2. Need for Mechanical Ventilation [ Time Frame: Anytime after randomization up to 36 weeks corrected gestational age ]
   Number of participants who required endotracheal intubation and mechanical ventilation
3. Total Ventilation Days [ Time Frame: After randomization up until hospital discharge ]
   Of those participants who required mechanical ventilation, the total number of days receiving ventilation
4. Necrotizing Enterocolitis (NEC) [ Time Frame: After randomization through hospital discharge ]
   Number of participants diagnosed with necrotizing enterocolitis
5. Symptomatic PDA Requiring Medical Treatment [ Time Frame: From randomization until discharge ]
   Number of participants with a symptomatic PDA that required medical treatment
6. Symptomatic PDA Requiring Surgical Ligation [ Time Frame: Randomization through discharge ]
   Number of participants with symptomatic PDA that required surgical ligation
7. Threshold Retinopathy of Prematurity (ROP) [ Time Frame: Randomization to discharge ]
   Threshold ROP defined as requiring interventional therapy
8. Severe Intracranial Hemorrhage [ Time Frame: Randomization to discharge ]
   Number of participants that developed severe intracranial hemorrhage (grade 3-4)
9. Sepsis [ Time Frame: Randomization to discharge ]
   Number of participants that developed sepsis

Other Outcome Measures:

1. Days in Hospital [ Time Frame: From birth to hospital discharge ]
   Length of stay of participants

Eligibility Criteria

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Ages Eligible for Study:	up to 72 Hours (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Birth weight of 500-1250 grams and gestational age of less than 34 weeks
• Age at enrollment is less than 72 hours
• Supplemental oxygen or 21% requirement by nasal cannula or NCPAP only

Exclusion Criteria:

• Presence of structural heart disease (other than patent ductus arteriosus, atrial septal defect less than 1 cm, or muscular ventricular septal defect less than 2 mm)
• Presence of lethal congenital anomaly
• Participating in another concurrent experimental study
• Requires mechanical ventilation in the first 72 hours of life (patients are not excluded if they are intubated briefly but they must be extubated at the time of consent and study entry prior to 72 hours of life)

Contacts and Locations

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Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35242
United States, California
University of California San Diego
San Diego, California, United States, 92123
United States, Colorado
Children's Hospital and University Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Illinois
Anne and Robert H. Lurie Children's Hospital of Chicago and Northwestern Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

University of Colorado, Denver

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	John Kinsella, MD	Chidlren's Hospital and University of Colorado Hospital

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kinsella JP, Cutter GR, Steinhorn RH, Nelin LD, Walsh WF, Finer NN, Abman SH. Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns. J Pediatr. 2014 Dec;165(6):1104-1108.e1. doi: 10.1016/j.jpeds.2014.06.018. Epub 2014 Jul 22.

Responsible Party:	University of Colorado, Denver
ClinicalTrials.gov Identifier:	NCT00955487 History of Changes
Other Study ID Numbers:	06-0124; 5P50HL084923 ( U.S. NIH Grant/Contract ); 5 P50 HL084923-030001
First Posted:	August 10, 2009
Results First Posted:	May 23, 2017
Last Update Posted:	June 15, 2017
Last Verified:	May 2017

Keywords provided by University of Colorado, Denver:

Premature Newborns; Inhaled Nitric Oxide

Additional relevant MeSH terms:

Premature Birth; Lung Diseases; Bronchopulmonary Dysplasia; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Respiratory Tract Diseases; Ventilator-Induced Lung Injury; Lung Injury; Infant, Premature, Diseases; Infant, Newborn, Diseases; Nitric Oxide; Bronchodilator Agents	Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters; Protective Agents